We have focused upon the genetic and molecular basis by which pathogenic microorganisms penetrate eucaryotic cells. Our studies show that the pathogenic Versinia share at least two distinct chromosomal loci, inv, and ail, that play a role in their entry into eucaryotic cells. The presence of ail sequences is correlated to an extraordinary degree with the clinical significance of Versinia enterocolitica isolates. We have also initiated a study to examine the capacity of Salmonella cholerasuis to invade and transcytose through polarized epithelial monolayers of Madin-Darby Canine Kidney (MDCK) cells requires active bacterial RNA and protein biosynthesis and was blocked by low temperature. Apical S cholerasuis infection resulted in an increase in paracellular permeability but the MDCK intercellular contacts were not significantly disrupted. Mutations affecting the ability of S. cholerasuis to adhere to, enter, and subsequently replicate within MDCK cells have been isolated by transposon insertion mutagenesis. Keywords: Bacterial invasion, Polarized animal cells.